It has recently been shown that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) has an effect in relation to bone anabolism indicating the potential use of this compound in the treatment of osteoporosis and conditions characterized by an abnormal bone mineralisation. Erben et al. (Endocrinology, 139, 4319–4328 (1998)) have provided evidence for a direct anabolic effect of 1,25(OH)2D3 on bone.
However, the therapeutic possibilities of 1,25(OH)2D3 in such indications are severely limited by the well known potent effect of this hormone on calcium metabolism; elevated blood concentrations will rapidly give rise to hypercalcemia. Thus, this compound is not completely satisfactory for use as a drug in the treatment of osteoporosis which may require prolonged administration of the drug in relatively high doses.
A number of oxa- and thia-analogues of vitamin D3 are known. 1α,25-dihydroxy-20-oxa-21-norvitamin D3 and 1α-hydroxy-20-oxa-21-norvitamin D3 are described in N. Kubodera et al., Chem. Pharm. Bull., 34, 2286 (1986), 1α,25-dihydroxy-22-oxavitamin D3 and 25-hydroxy-22-oxavitamin D3 are described in E. Murayama et al., Chem. Pharm. Bull., 34, 4410 (1986), J. Abe et al., FEBS LETTERS, 226, 58 (1987) and European Patent Application, publication number 184 112, and 1α,25-dihydroxy-23-oxavitamin D3 and 1α,25-dihydroxy-23-thiavitamin D3 are described in European Patent Application publication number 78704. 24- and 25-sulphonyl-analogues of 1α,25-dihydroxy-vitamin D3 have been described in G. H. Posner et al., J. Med. Chem., 42, 3425 (1999).
Some of these compounds may have advantages over 1,25(OH)2D3 in having reduced calcium metabolism effects relative to 1,25(OH)2D3. However, there is no report on a possible effect of these compounds in relation to bone anabolism.